Multiple sclerosis (MS) affects some 2.3 million people worldwide, with 80% experiencing inflammation in the cerebellum, a brain region crucial for movement and balance. This inflammation can lead to tremors, poor coordination, and motor control issues, which often worsen over time due to the loss of healthy brain tissue.
Researchers at the University of California, Riverside, have made a significant discovery about the underlying mechanisms of cerebellar degeneration in MS. Their study, published in PNAS, suggests that mitochondrial dysfunction may play a key role in the progressive loss of Purkinje cells and worsening motor impairments.
Purkinje cells are essential for coordinating smooth movements and balance. In MS, these cells can be damaged, leading to problems with coordination and movement, known as ataxia. The study found that Purkinje cells in MS patients had fewer branches, lost myelin, and experienced mitochondrial problems, resulting in a failing energy supply.
“Our study, conducted by my graduate student Kelley Atkinson, proposes that inflammation and demyelination in the cerebellum disrupt mitochondrial function, contributing to nerve damage and Purkinje cell loss,” said Seema Tiwari-Woodruff, a professor of biomedical sciences in the UC Riverside School of Medicine, who led the research team. “We observed a significant loss of the mitochondrial protein COXIV in demyelinated Purkinje cells, suggesting that mitochondrial impairment contributes directly to cell death and cerebellar damage.”
The research team used a mouse model of MS to investigate mitochondrial alterations during disease progression. They found that the mice lost Purkinje cells over time, similar to people with MS. The loss of energy seemed to be a key part of MS, with cells only dying later.
“Our research looked at brain tissue from MS patients and found major issues in these neurons: they had fewer branches, were losing myelin, and had mitochondrial problems – meaning their energy supply was failing,” Tiwari-Woodruff said. “Because Purkinje cells play such a central role in movement, their loss can cause serious mobility issues. Understanding why they’re damaged in MS could help us find better treatments to protect movement and balance in people with the disease.”
The study suggests that targeting mitochondrial health may be a promising strategy to slow or prevent neurological decline and improve quality of life for people living with MS.
The researchers plan to further investigate whether mitochondrial impairment affects other brain cells, such as oligodendrocytes and astrocytes. This research has the potential to open the door to finding ways to protect the brain early on, such as boosting energy in brain cells or aiding repair of the myelin sheaths.
